DTU Chemistry

Finally Unveiled: Structure of Enzyme that Converts Dopamine to Norepinephrine

Friday 08 Apr 16
After decades of research, scientists from DTU Chemistry have identified the first structure of the enzyme that controls conversion between two of our body’s most important neurotransmitters, dopamine and norepinephrine.

A fascinating view and insight of the enzyme dopamine β-hydroxylase

The finding could lead to the development of targeted treatments for a wide range of diseases, including depression and anxiety, post-traumatic stress disorder, Parkinson’s disease, congestive heart failure, schizophrenia, and Alzheimer’s.

Dopamine and norepinephrine play a major role in regulating traits like memory, mood, and behavior. The enzyme dopamine β-hydroxylase – a member of a small, unique class of enzymes  - plays a critical role in biosynthesis of neurotransmitters and hormones and controls the conversion between dopamine and norepinephrine, and thus the levels of these two transmitters in our body.

This enzyme has been linked to a number of disorders, including those mentioned above, yet the structure of dopamine β-hydroxylase has not yet been elucidated.

Using X-ray crystallography, a team lead by Associate Professor Hans E.M. Christensen at DTU Chemistry, report the crystal structure of human dopamine β-hydroxylase, finding that the enzyme contains two new potential binding sites.

Hans Erik Mølager Christensen - foto:A.Frejberg

Together with Associate Professor Pernille Harris, DTU Chemistry, Trine Vendelboe and colleagues from the University of Oxford, the team also found that dopamine β-hydroxylase seems to function by a flip-flop mechanism, where one half of the enzyme carries out the enzymatic reaction, while the other half of the enzyme unloads the product (norepinephrine) and loads new substrate (dopamine). Then, the enzyme flip-flops and the function of the two halves of the enzyme are interchanged.

Further understanding of this potential flip-flop mechanism may provide new insights into the numerous disorders associated with dopamine.

Read more about Hans E M Christensen's research in Metalloprotein Chemistry.

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